Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF. / Dichtl, Stefanie; Sanin, David E; Koss, Carolin K; Willenborg, Sebastian; Petzold, Andreas; Tanzer, Maria C; Dahl, Andreas; Kabat, Agnieszka M; Lindenthal, Laura; Zeitler, Leonie; Satzinger, Sabrina; Strasser, Alexander; Mann, Matthias; Roers, Axel; Eming, Sabine A; El Kasmi, Karim C; Pearce, Edward J; Murray, Peter J.

In: Life Science Alliance, Vol. 5, No. 4, 04.2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Dichtl, S, Sanin, DE, Koss, CK, Willenborg, S, Petzold, A, Tanzer, MC, Dahl, A, Kabat, AM, Lindenthal, L, Zeitler, L, Satzinger, S, Strasser, A, Mann, M, Roers, A, Eming, SA, El Kasmi, KC, Pearce, EJ & Murray, PJ 2022, 'Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF', Life Science Alliance, vol. 5, no. 4. https://doi.org/10.26508/lsa.202101315

APA

Dichtl, S., Sanin, D. E., Koss, C. K., Willenborg, S., Petzold, A., Tanzer, M. C., Dahl, A., Kabat, A. M., Lindenthal, L., Zeitler, L., Satzinger, S., Strasser, A., Mann, M., Roers, A., Eming, S. A., El Kasmi, K. C., Pearce, E. J., & Murray, P. J. (2022). Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF. Life Science Alliance, 5(4). https://doi.org/10.26508/lsa.202101315

Vancouver

Dichtl S, Sanin DE, Koss CK, Willenborg S, Petzold A, Tanzer MC et al. Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF. Life Science Alliance. 2022 Apr;5(4). https://doi.org/10.26508/lsa.202101315

Author

Dichtl, Stefanie ; Sanin, David E ; Koss, Carolin K ; Willenborg, Sebastian ; Petzold, Andreas ; Tanzer, Maria C ; Dahl, Andreas ; Kabat, Agnieszka M ; Lindenthal, Laura ; Zeitler, Leonie ; Satzinger, Sabrina ; Strasser, Alexander ; Mann, Matthias ; Roers, Axel ; Eming, Sabine A ; El Kasmi, Karim C ; Pearce, Edward J ; Murray, Peter J. / Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF. In: Life Science Alliance. 2022 ; Vol. 5, No. 4.

Bibtex

@article{5fa09fce14ec4beb87f207ceaf621789,

title = "Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF",

abstract = "Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn's Disease. Previously, we and others found that TNF blocks the emergence and function of alternative-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balance of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages, we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis, and signaling pathway deconvolution. We found that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way, dependent on JNK signaling via the type 1 TNF receptor on specific populations of alternative-activated macrophages. We further determined that JNK signaling has a profound and broad effect on activated macrophage gene expression. Our findings suggest that TNF's anti-M2 effects evolved to specifically modulate components of tissue and reparative M2 macrophages and TNF is therefore a context-specific modulator of M2 macrophages rather than a pan-M2 inhibitor.",

keywords = "Animals, Cells, Cultured, Cytokines/metabolism, Female, Macrophage Activation/drug effects, Macrophages/drug effects, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Signal Transduction/drug effects, Transcription, Genetic/drug effects, Tumor Necrosis Factor Inhibitors/pharmacology, Tumor Necrosis Factor-alpha/metabolism",

author = "Stefanie Dichtl and Sanin, {David E} and Koss, {Carolin K} and Sebastian Willenborg and Andreas Petzold and Tanzer, {Maria C} and Andreas Dahl and Kabat, {Agnieszka M} and Laura Lindenthal and Leonie Zeitler and Sabrina Satzinger and Alexander Strasser and Matthias Mann and Axel Roers and Eming, {Sabine A} and {El Kasmi}, {Karim C} and Pearce, {Edward J} and Murray, {Peter J}",

note = "{\textcopyright} 2022 Dichtl et al.",

year = "2022",

month = apr,

doi = "10.26508/lsa.202101315",

language = "English",

volume = "5",

journal = "Life Science Alliance",

issn = "2575-1077",

publisher = "Life Science Alliance",

number = "4",

}

RIS

TY - JOUR

T1 - Gene-selective transcription promotes the inhibition of tissue reparative macrophages by TNF

AU - Dichtl, Stefanie

AU - Sanin, David E

AU - Koss, Carolin K

AU - Willenborg, Sebastian

AU - Petzold, Andreas

AU - Tanzer, Maria C

AU - Dahl, Andreas

AU - Kabat, Agnieszka M

AU - Lindenthal, Laura

AU - Zeitler, Leonie

AU - Satzinger, Sabrina

AU - Strasser, Alexander

AU - Mann, Matthias

AU - Roers, Axel

AU - Eming, Sabine A

AU - El Kasmi, Karim C

AU - Pearce, Edward J

AU - Murray, Peter J

PY - 2022/4

Y1 - 2022/4

N2 - Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn's Disease. Previously, we and others found that TNF blocks the emergence and function of alternative-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balance of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages, we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis, and signaling pathway deconvolution. We found that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way, dependent on JNK signaling via the type 1 TNF receptor on specific populations of alternative-activated macrophages. We further determined that JNK signaling has a profound and broad effect on activated macrophage gene expression. Our findings suggest that TNF's anti-M2 effects evolved to specifically modulate components of tissue and reparative M2 macrophages and TNF is therefore a context-specific modulator of M2 macrophages rather than a pan-M2 inhibitor.

AB - Anti-TNF therapies are a core anti-inflammatory approach for chronic diseases such as rheumatoid arthritis and Crohn's Disease. Previously, we and others found that TNF blocks the emergence and function of alternative-activated or M2 macrophages involved in wound healing and tissue-reparative functions. Conceivably, anti-TNF drugs could mediate their protective effects in part by an altered balance of macrophage activity. To understand the mechanistic basis of how TNF regulates tissue-reparative macrophages, we used RNAseq, scRNAseq, ATACseq, time-resolved phospho-proteomics, gene-specific approaches, metabolic analysis, and signaling pathway deconvolution. We found that TNF controls tissue-reparative macrophage gene expression in a highly gene-specific way, dependent on JNK signaling via the type 1 TNF receptor on specific populations of alternative-activated macrophages. We further determined that JNK signaling has a profound and broad effect on activated macrophage gene expression. Our findings suggest that TNF's anti-M2 effects evolved to specifically modulate components of tissue and reparative M2 macrophages and TNF is therefore a context-specific modulator of M2 macrophages rather than a pan-M2 inhibitor.

KW - Animals

KW - Cells, Cultured

KW - Cytokines/metabolism

KW - Female

KW - Macrophage Activation/drug effects

KW - Macrophages/drug effects

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Signal Transduction/drug effects

KW - Transcription, Genetic/drug effects

KW - Tumor Necrosis Factor Inhibitors/pharmacology

KW - Tumor Necrosis Factor-alpha/metabolism

U2 - 10.26508/lsa.202101315

DO - 10.26508/lsa.202101315

M3 - Journal article

C2 - 35027468

VL - 5

JO - Life Science Alliance

JF - Life Science Alliance

SN - 2575-1077

IS - 4

ER -

ID: 303114298